The present invention relates to a process and a device for making liquid dosage formulations on demand from tablets and capsules, and the compositions produced therefrom.
For several categories of patients, both human and veterinary, the use of tablets and capsules for administering medicinal compounds is not feasible. Some patients are unable to ingest tablets and capsules in a single and smooth swallowing motion, or lack the desire to ingest such dosage forms. Also, some tablets and capsules have an unpleasant taste or an uncomfortable or unpleasant size. Patient populations who encounter such problems include the elderly, particularly those in nursing homes, pediatric patients and patients who have encountered severe trauma due to surgery or involvement in accidents. Also, animals often will not or cannot swallow tablets or capsules. In the text that follows, the term xe2x80x9cpatientxe2x80x9d refers to humans and animals.
In such situations, health care providers desire alternative dosage forms, especially liquids. For the above listed patient populations, liquid formulations are in general easier to swallow. If a liquid dosage alternative is commercially available, health care providers can avail themselves of the product for administration to their patients.
However, in many cases a liquid dosage form is not commercially available or, in some instances, the commercially available liquid dosage product is not suitable for the patient. In such circumstances, health care providers are forced to improvise and prepare liquid products in an extemporaneous fashion. Common approaches include grinding tablets in a mortar and pestle and adding the resultant powder to an excipient such as applesauce or a suitable fruit juice. In the case of capsules, the shells are separated and the enclosed powder added to an available excipient. The resultant mixture is then administered to the patient. Although this accomplishes the objective of providing a medicament formulation to the patient, the process does not guarantee the achievement of two important objectives, namely, delivery of the total dosage to the patient and avoidance of cross-contamination.
The first desired objective is the delivery of the total desired dose of the medicinal compound contained in the tablet or capsule to the patient. For example, some of the medicinal compound may be lost as the crushed tablet is transferred between a mortar and pestle to the dosing cups containing the excipient. In addition, improperly designed dosing procedures can result in the patient receiving less than the total dose. For example, the patient may not ingest all of the excipient/drug mixture. Medicinal compounds also are subject to decomposition. In certain instances, the decomposition accelerates when the material is in a liquid. The uncontrolled decomposition of the medicinal compound in an extemporaneously prepared liquid formulation could add to a reduction in the effective dose. In addition, the patient could be exposed to various undesired decomposition products.
Another problem with the present ad hoc approach to preparing liquid formulations is that some patients still resist taking the full dosage amount because of the unpleasant taste of the composition. For example, the active medicaments in cold medications often have a very unpleasant taste that is not easily masked by lightly flavored fruit drinks and sauces. Therefore, measures must be taken to flavor the liquid in some way so as to taste-mask the active medicament and prevent its rejection by the patient. If these drawbacks are not resolved, high degrees of patient compliance cannot be assured.
The second objective of the present invention is avoidance of medicament cross-contamination. The preparation of several extemporaneous formulations in a common environment demands the scrupulous cleaning and washing of the apparatus used in preparing the formulation. This is a difficult and cumbersome task especially for medicinal compounds that are not readily soluble in aqueous media. The cleaning requires well-documented research to ensure that the process is both complete and reproducible. Most health care providers do not have facilities and personnel to conduct the necessary research and experimentation. Cross-contamination can result in major side effects especially when the contaminant is a medicinal compound with a low therapeutic index.
In addition, the patients receiving these extemporaneously formulated products generally are those who would be harmed the most from cross-contamination. For example, pediatric and geriatric patients are more sensitive to small amounts of medicament, such as that present by contamination, than a typical adult patient. As a useful comparison, manufacturing operations in pharmaceutical companies often utilize safety factors of less than from {fraction (1/100)}th to {fraction (1/1000)}th of the human dose of a medicinal compound as a guideline in controlling cross-contamination between products. This low tolerance for cross-contamination is evidence of the acceptance in the pharmaceutical industry of the problems and risks associated with even small amounts of medicament cross-contamination.
The invention described herein provides an easy and convenient solution for providing extemporaneously compounded liquid products from tablets, capsules and other solid or gel pharmaceutical dosage forms (collectively xe2x80x9csolid dosage formsxe2x80x9d), preferably which are commercially available. Under the process of the invention, a health care provider or patient has the ability to administer a complete drug dose in a palatable liquid product and to eliminate cross-contamination. The compounding of the liquid formulation and the dosing of the resultant product are undertaken in a sanitary, reproducible and convenient fashion.
The invention relates to a process and device for making liquid dosage formulations on demand from solid dosage forms, and the pharmaceutical compositions produced therefrom. The device comprises a mixing and dosing cup (1) having an abrasive interior surface (2). According to the process of the invention, a liquid dosage formulation is prepared by combining a solid dosage form of a pharmaceutical medicament and an aqueous diluent in a mixing and dosing cup having an abrasive surface, agitating the resulting mixture, and administering the resulting liquid dosage formulation to a patient in the mixing and dosing cup (1). The mixing and dosing cup (1) is a single-use cup, meaning it is not used again for pharmaceutical dosaging or mixing.